Faculty of Medicine
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Item type:Publication, Small and large cell neuroendocrine carcinomas of the uterine cervix. A report of 10 cases.(Springer, 2005-08) ;Kubelka-Sabit, Katerina ;Plaseska-Karanfilska, Dijana ;Prodanova, Irina ;Yashar, GenghisHadzi-Nicheva, BiljanaBACKGROUND: Small (SCC) and large cell (LCC) neuroendocrine carcinomas of the uterine cervix are rare and highly aggressive neoplasms. Their association with the integration of human papilloma virus (HPV) DNA of the types 16 or 18 has been documented in many studies. AIMS: The purpose of this study is to present the clinical, histopathological, immunohistochemical characteristics and the presence of HPV DNA in ten cases of SCCs and LCCs of the uterine cervix. METHODS: Seven patients with primary SCCs and three patients with LCCs of the uterine cervix were diagnosed at our department between 1989 and 2004. Clinical data were retrieved from the patients’ files and included age, recurrence and survival. Routinely processed operative and/or biopsy specimens were used for immunohistochemical stains and hybridization procedures. Primary antibodies against several epithelial, neuroendocrine, mesenchimal and proliferative markers were included. The presence of HPV DNA was assessed by conventional in situ hybridization (ISH) using probes for HPV 16/18 and 31/33/51 and polymerase chain reaction (PCR), using three primers (MY09/11, GP5+/GP6+, E6). Six of the patients were surgically treated. Postoperatively, four received chemo and/or radiotherapy, two rejected further treatment and one patient was lost to follow-up. The other four patients underwent conservative treatment due to advanced disease. RESULTS: The patients’ age ranged from 25 to 71 years. Histologically, the tumors showed trabecular, nesting or a sheet-like pattern, with areas of necrosis and frequent mitoses. Their neuroendocrine nature was confirmed by diffuse positive immunostaining for neuron-specific enolase and low-molecular weight cytokeratins. Focal positivity for chromogranin, synaptophysin and S100, together with pancytokeratin and EMA, was evident in the majority of the tumors. Their aggressive potential was confirmed by high Ki-67 proliferative index (50-90%). HPV types 16/18 were found in 4 tumors using ISH, and HPV 16 in additional 3, using PCR (type 16). 3 of the patients developed distant metastases and died 7-48 months after receiving partial or full treatment, while 6 are alive and without evidence of disease after 4-38 months. CONCLUSIONS: SCCs and LCCs are highly aggressive neoplasms. However, early diagnosis and combined therapy may improve survival in some patients. Although mainly a morphologic diagnosis, immunohistochemistry may help in the diagnosis of SCC and LCC. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Blood vessel invasion and inflammatory stromal reaction at the invasion front as additional significant prognostic factors in surgically treated patients with cervical carcinoma.(Springer, 2001-09); ;Yashar, Genghis ;Veljanoska, Slavica ;Kubelka, KaterinaProdanova, IrinaIntroduction: The objective of this study was to evaluate the prognostic significance of 23 clinical and histopathological variables in relation to disease-free (DFS) and overall survival (OS) in patients with early stage cervical carcinomas. Methods: A retrospective analysis of 237 patients with cervical carcinoma, undergoing radical hysterectomy and postoperative irradiation between 1988 and 1997 was conducted. The operative specimens were subjected to detailed and uniform histopathological work-up. The patients were staged according to the postoperative TNM classification of UICC (1997) guidelines. Mean follow-up time was 57 (18-124) months. Results: The 5 and 10-year OS rate was 80.8%, while DFS rates at 5 and 10 years were 76.8% and 75.5%, respectively. In multivariate analysis, blood vessel invasion, pelvic lymph node metastases, tumor diameter, inflammatory stromal reaction at the invasion front, and minimum thickness of uninvolved cervical stroma/parametrial extension, were independent and significant variables. The prognostic index, as an indicator of the patient's place in the prognostic spectrum, defined by the Cox regression model, was able to categorize the patients into three distinct risk groups. The 5-year DFS and OS rates of the low-, intermediate-, and high-risk groups were 97.5%, 86.3%, and 43.8%, vs. 98.8%, 84.5%, and 45.3%, respectively (P<0.0001). Conclusions: The prognostic index could be a sound basis for an appropriate planning of the following therapeutical strategy for the surgically treated patients with cervical carcinoma. The postoperative TNM classification should be modified, incorporating the blood vessel invasion and the inflammatory stromal reaction at the invasion front, as additional significant prognostic factors. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Примарен малигнен меланом на грлото на матката - приказ на случај(Македонско лекарско друштво = Macedonian medical association, 2001) ;Veljanoska, Slavica ;Arsovski, Oliver; ;Tolevska, CvetaПримарниот малигнен меланом на грлото на матката е ретко заболување. Клиничката слика е мошне неспецифична и не се разликува од онаа на вообичаените симптоми на порциото. Се манифестира со контактни, а подоцна во текот на болеста и спонтани вагинални крварења, односно во напреднатите стадиуми и со симптоми од дисеминација на процесот. Самото дијагностицирање на овој ентитет бара огромно внимание, особено во разграничувањето на ПММГМ од метастаза на меланом на грлото на матката. Недвосмислен доказ за постоење на ПММГМ е неговата хистопатолошка верификација во преодниот епител. Кај ПММГМ се јавува и проблем при одредување на стадиумот на болеста, но сепак повеќето автори го користат FIGO системот наспроти критериумите за одредување на стадиумите кај кутаниот малигнен меланом според Clark и Breslow. Радикалната хистеректомија според Wertheim Meigs и адјувантната хемиотерапија се методи на избор во третманот на ПММГМ. Примарниот меланом на вратот на матката кој се дијагностицира во напреднат стадиум на болеста (иноперабилен) покажува резистенција на било каков вид на конзервативна терапија, со тенденција за брза локална и системска прогресија на болеста, што резултира со исклучително лоша прогноза. Primary malignant melanoma of the uterine cervix (PMMUC) is an extremely rare disease. Clinical presentation of PMMUC is not specific and not different from the common cervical malignancies. It presentс with postcoital spotting, spontaneous vaginal bleeding, even with the signs of dissemination in the advanced stages of the disease. The diagnosis is difficult, because it is essential to differentiate PMMUC from secondary malignant melanoma, by the presence of melanocytes in the epithelium and verification of junctional activities. There is a consensus about staging procedure using FIGO criteria, rather than that of Clark and Breslow (TNM clasification, UICC). Radical hysterectomy is accepted as the most important initial approach, while the role of pelvic lymphadenectomy remains unclear. We present a case of PMMUC in advanced, inoperable stage of the disease, treated in our institution by radiotherapy and chemotherapy. There was no response to any available conservative treatment.
